We will determine the changes in DNA base sequence produced by the action of various mutagens on lambda bacteriophage. The phage will be mutagenized as free virus particles in solution (as infective DNA in solution if necessary), as plasmids inside E. coli host cells, and as prophage integrated into cell genomes. Mutants in specific loci, e.g. cI, will be mapped to determine those which fall into selected DNA restriction fragments. These fragments will be isolated and sequenced. Mutagens chosen for study will initially be those thought or suspected of producing specific sequence changes-transitions, transversion, frameshifts, and large deletions (or insertions). A knowledge of the specificities should provide useful tools for molecular geneticists. The results will be used to evaluate proposed enzymatic mechanisms and to suggest new ones. Later, sequence changes will be determined for mutagens (and carcinogens) of practical importance such as ionizing radiations. The changes in DNA base sequence will predict changes in amino acid sequence, which will be related to loss of repressor function (lack of change in function for "silent" mutations).